6PVH
Crystal structure of PhqK in complex with paraherquamide K
Summary for 6PVH
| Entry DOI | 10.2210/pdb6pvh/pdb |
| Descriptor | FAD monooxygenase, (7aS,12S,12aR,13aS)-3,3,12,14,14-pentamethyl-3,7,11,12,13,13a,14,15-octahydro-8H,10H-7a,12a-(epiminomethano)indolizino[6,7-h]pyrano[3,2-a]carbazol-16-one, FLAVIN-ADENINE DINUCLEOTIDE, ... (4 entities in total) |
| Functional Keywords | monooxygenase, flavin, biosynthetic protein |
| Biological source | Penicillium fellutanum |
| Total number of polymer chains | 1 |
| Total formula weight | 52562.17 |
| Authors | Fraley, A.E.,Smith, J.L.,Sherman, D.H. (deposition date: 2019-07-20, release date: 2020-01-22, Last modification date: 2024-03-13) |
| Primary citation | Fraley, A.E.,Caddell Haatveit, K.,Ye, Y.,Kelly, S.P.,Newmister, S.A.,Yu, F.,Williams, R.M.,Smith, J.L.,Houk, K.N.,Sherman, D.H. Molecular Basis for Spirocycle Formation in the Paraherquamide Biosynthetic Pathway. J.Am.Chem.Soc., 142:2244-2252, 2020 Cited by PubMed Abstract: The paraherquamides are potent anthelmintic natural products with complex heptacyclic scaffolds. One key feature of these molecules is the spiro-oxindole moiety that lends a strained three-dimensional architecture to these structures. The flavin monooxygenase PhqK was found to catalyze spirocycle formation through two parallel pathways in the biosynthesis of paraherquamides A and G. Two new paraherquamides (K and L) were isolated from a Δ strain of , and subsequent enzymatic reactions with these compounds generated two additional metabolites, paraherquamides M and N. Crystal structures of PhqK in complex with various substrates provided a foundation for mechanistic analyses and computational studies. While it is evident that PhqK can react with various substrates, reaction kinetics and molecular dynamics simulations indicated that the dioxepin-containing paraherquamide L is the favored substrate. Through this effort, we have elucidated a key step in the biosynthesis of the paraherquamides and provided a rationale for the selective spirocyclization of these powerful anthelmintic agents. PubMed: 31904957DOI: 10.1021/jacs.9b09070 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.89 Å) |
Structure validation
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